Treatment for selective weight control

ABSTRACT

A treatment for accelerating regional weight reduction in humans, wherein an active ingredient encouraging elimination of fatty deposits, preferably a beta adrenergic stimulator or an alpha-2 adrenergic inhibitor, is selectively delivered to a regional fat deposit prior to commencing or during a general weight control program, whereby body weight is preferentially reduced in the selected area. The beta adrenergic stimulator, preferably isoproterenol or forskolin, or the alpha-2 adrenergic inhibitor, preferably yohimbine, or combinations thereof may be delivered by any means accomplishing specific delivery to the selected area, including injection, implantation, and topical application to the skin as in an ointment or creme.

BACKGROUND OF THE INVENTION

This invention relates to control of weight loss in humans, and moreparticularly, to a process wherein weight loss is achieved from selectedportions of the body by reduction of regional fat deposits.

When an overweight person reduces body weight through a weight controlprogram, it is often observed that the excess body fat is removed morerapidly from some parts of the body than from other parts. For example,weight loss tends to be more rapid from the abdomen than from thethighs. For a person who loses only a relatively small amount of weight,such differential weight loss during the reduction program is notnoticeable. However, overweight persons who must lose larger amounts ofweight may be distressed by the failure to achieve normal bodilyproportions during the weight control program. Most of the weight lossmay come from the abdomen and chest, while the thighs remain excessivelyoverweight. This result is undesirable aesthetically andpsychologically, in that the body neither attains proper proportions noris perceived to approach proper proportions. Additionally, the fattydeposits of the thighs which remain may have a rumpled or"peau-de-orange" appearance, popularly termed "cellulite, " which isunattractive and may be particularly distressing. Thus, there exists asignificant problem arising in weight control programs as a result ofthe differential reduction in body fat deposits.

Two approaches have generally been taken to alleviate the problemcreated by the differential weight loss in weight control programs. Inone, the weight loss program is carried to extremes so that the personloses a greater amount of weight than is medically desirable, andeventually weight is lost from all portions of the body. Such excessiveweight loss may result in poor health, and still not obtain a desirablephysical appearance. In a second commonly used method, the personundergoing weight loss seeks to selectively eliminate remaining fatdeposits through an exercise or physical motion program. For example,the thighs may be massaged or vibrated in an attempt to eliminate thefatty deposits thereon. However, such physical weight loss programs arenot feasible for all persons and are of questionable effectiveness.

Accordingly, there has been a continuing need for a reliable, effectivetreatment for accomplishing the selective reduction of regional body fatdeposits during a weight control program by accelerating weight loss inareas such as the thighs which normally reduce less rapidly than theabdomen. The present invention fulfills this need, and further providesrelated advantages.

SUMMARY OF THE INVENTION

The present invention provides a treatment method for achieving aselective loss in body weight during a weight control program, by theselective reduction of regional body fat deposits. Thus, the reductionof those fatty deposits located in areas which normally reduce moreslowly may be accelerated. With this invention, a person undergoing aweight control program may achieve a desirable balanced rate of weightloss.

In accordance with the invention, an active ingredient encouragingreduction of fat cells is selectively delivered to a portion of the bodywhere weight reduction is desired, so that accelerated reduction of theregional body fat deposit occurs during a general weight controlprogram, thereby achieving a balanced weight reduction. Preferred activeingredients found useful in accomplishing accelerated reduction ofregional body fat deposits include beta adrenergic stimulators, alpha-2adrenergic inhibitors, and combinations thereof, most preferably thebeta adrenergic stimulator isoproterenol. The active ingredient may bedelivered to the regional fatty deposit by any means which allowsspecific delivery, rather than nonspecific delivery, including but notlimited to injection, implantation and topical application to the skinin an ointment or creme, for example.

It will be appreciated from the foregoing that the present inventionrepresents a significant advance in control of overweight conditions.With this invention, enhanced reduction of those regional body fatdeposits which normally are reduced more slowly during a weight controlprogram is achieved. As a result, the person undergoing a weight controlprogram more rapidly achieves a normal body appearance in a medicallyacceptable manner.

Other features and advantages of the present invention will becomeapparent from the following more detailed description of the preferredembodiment, which describes, by way of example, the principles of theinvention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention is embodied in a treatment used in conjunctionwith a general weight loss program, whereby a reduction in regional bodyfat deposits is selectively accelerated during a general weight controlprogram. In a general weight control program, as that term is usedherein, a person seeks to achieve a loss of body weight, normally by acombination of a calorie-restricted diet and exercise. In successfulweight control programs, it is often noticed that weight loss occursmore rapidly from certain parts of the body than from other parts, andspecifically weight loss tends to be more rapid from the abdomen thanfrom the thighs, at least in part because the fatty deposits in thethighs exhibit a greater resistance to reduction than do the fattydeposits in the abdomen.

In accordance with the invention, an active ingredient encouragingreduction of fatty tissue is selectively delivered to a portion of thebody having a regional body fat deposit, so that a selectiveacceleration in reduction of the regional body fat deposit is achievedduring the general weight control program. Preferred active ingredientsin accomplishing selective reduction of regional body fat depositsinclude beta adrenergic stimulators and alpha-2 adrenergic inhibitors,or combinations thereof, most preferably the beta adrenergic stimulatorisoproterenol. The active ingredient may be delivered to the fattydeposit be any specific means which allows selective localized delivery,rather than a nonspecific delivery, including but not limited toinjection, implantation and topical application to the skin in anointment or creme.

The fat deposits on an overweight person are observed to be concentratedin particular parts of the body rather than uniformly throughout thebody. Concentrated local fat deposits, termed herein regional fatdeposits, are typically found in the abdomen and thighs of an overweightperson. During a general weight control program, as may be conductedwith or without a doctor's care, it is observed that weight is not lostat uniform rates from all of the regional fat deposits. Instead, weightis ordinarily lost more rapidly from the abdomen than from the thighsand hips, so that the thighs and hips may remain disproportionatelylarge even as the abdomen approaches a normal condition.

The medical explanation for the differential weight loss phenomenon isnot fully settled. While applicant does not wish to be bound by thispossible explanation, it is believed that such differential weight lossresults from variations in the rates of lipogenesis and lipolysis withineach body location during the weight control program. Lipolysis isapparently mediated in part by the nervous system through action on thebeta adrenergic and alpha-2 adrenergic receptors in the fat cells.Previous in vitro studies of adipose tissue excised from persons beforeand during weight control programs have shown that thigh and abdominaltissue respond differently to drugs known to work through beta andalpha-2 adrenergic receptors. For example, it has been shown in vitrothat the lipolytic effect of catecholamines is greater in abdominal fatthan in thigh fat, and conversely the antilipolytic effect of insulin isless marked in abdominal fat than in thigh fat. Such studies, while ofinterest in understanding the problem, provide no suggestion for an invivo treatment to overcome this condition.

The in vivo neurological control of lipolysis in the fat cell isorganized such that activity of the beta adrenergic receptor stimulateslipolysis, while activity of the alpha-2 adrenergic receptor inhibitslipolysis. An agent which activates the beta adrenergic receptorencourages lipolysis, or reduction in size, of the fat cell, while anagent which activates the alpha-2 adrenergic receptor discourageslipolysis of the fat cell. Conversely, in respect of the blocking oflipolysis, an agent which inhibits the alpha-2 adrenergic receptorshould encourage lipolysis of the fat cell by reducing blocking effects.Therefore, a beta adrenergic stimulator or an alpha-2 adrenergicinhibitor, or combinations thereof, encourages lipolysis of a fat cell.Additionally, an alpha-2 adrenergic inhibitor may allow lipolysis evenin the presence of a drug which stimulates both the beta and alpha-2adrenergic receptors.

To counteract the greater responsiveness of the fat cells in the abdomento the lipolytic effects of beta adrenergic stimulation. Applicants havefound that in vivo selective delivery and application of activeingredients to regional fat deposits can reduce those depositspreferentially during a weight control program. Specifically, localdelivery of a beta adrenergic stimulator encourages lipolysis of fatcells which normally undergo lipolysis only slowly. Local delivery of anincreased concentration of an alpha-2 adrenergic inhibitor has a similareffect, for the reason that inhibition of lipolysis is blocked. Examplesof known beta adrenergic stimulators include, but are not limited to,theophylline, isoproterenol, forskolin and epinephrine. Examples ofknown alpha-2 adrenergic inhibitors include, but are not limited to,yohimbine, rauwolscine, piperoxane, phentholamine and dihydroergotamine.

Successful selective reduction of fat cell deposits requires that thebeta adrenergic stimulator, the alpha-2 adrenergic inhibitor, orcombinations thereof, be specifically delivered to the fatty deposit forwhich lipolysis is sought. It is believed that a nonspecific deliverythroughout the body would result in stimulation of lipolysis in allparts of the body, so that abdominal weight loss would exceed weightloss of the thighs, for example. (The systemic effects of generalinfusions are discussed in Goodman and Gilman's "The PharmacologicalBasis of Therapeutics", 6th ed., editors Alfred Goodman Gilman, Lewis S.Goodman and Alfred Gilman, Mcmillen Publishing Co., 1980 at pages149-154.)

Specific delivery of the active ingredient which encourages lipolysis ofthe fat cells may be accomplished by any means whereby a higherconcentration is achieved in a specific region of the body. Examples ofacceptable delivery systems include injections with a needle andsyringe, injections with an air gun, surgical implantation below thesurface of the skin, and topical application to the surface of the skinover the regional fat deposit, such as by ointments and creams. Afterdelivery, diffusion of the active ingredient throughout the regional fatdeposit may be aided by heating or massaging of the deposit, or similarprocedures.

While it is possible for the active ingredient to be administered as araw chemical, it is preferable to present it as a pharmaceuticalformulation preparation. Such a formulation, within the scope of thepresent invention, can comprise a chemical which encourages lipolysis ofthe fat cell such as a beta adrenergic stimulator or an alpha-2adrenergic inhibitor, as above described, together with one or moreacceptable carriers therefor and optionally other therapeuticingredients. The carrier(s) must be "acceptable " in the sense of beingcompatible with other ingredients of the formulation and not deleteriousto the recipient thereof. The formulations should be suitable for localdelivery as specified above. Thus, it is understood that the treatmentdescribed herein may include the step of bringing into association theactive ingredient with a liquid carrier, and then locally delivering theformulation as specified above. Formulations suitable for administrationconveniently comprise sterile aqueous solutions of the active chemical,which may be conveniently prepared by mixing the acitve chemical withwater, and after rendering said solution sterile it may be presented insealed containers.

As described in the example presented below, one effective deliverysystem for the active ingredient is a sterile saline solution. Such asolution may be delivered to a selected regional fat deposit by one ormore injections of such a solution directly into the deposit. Anotherdelivery system would be the preparation of an ointment or creamcontaining an active ingredient therein. For example, a beta adrenergicstimulator such as forskolin and an alpha-2 adrenergic inhibitor such asyohimbine may be mixed together in any of a number of suitable ointmentbases known to pharmacologists, such as Aquaphor, and applied topicallyto the surface of the skin above the regional fat deposit whosereduction is to be accelerated. One acceptable ointment would deliverabout 1.2 ×10⁻⁹ molar forskolin and about 25 ×10³¹ 6 molar yohimbine asactive ingredients to the fat deposit, although other active ingredientsand treatment levels would also be acceptable. To deliver this level ofactive ingredient, higher concentrations in the ointment may berequired.

The following examples will serve to illustrate the application of thepresent invention. Five obese outpatient women who were displeased withtheir heavy thighs received injections of 0.2 cubic centimeters of a10⁻⁵ molar sterile saline solution of isoproterenol every four cm aroundthe entire circumference of one thigh each. (Initial studies suggestedthat the diffusional distance of the active ingredient in such atreatment is about 2 cm. The total amount of injected drug had noobservable effect systematically in symptoms, pulse rate, or bloodpressure in this intitial study on one patient, as the total dosage inthis treatment is at a very low level.) The injections were positionedtwo-thirds of the distance from the greater trochanter to the knee usinga one-half inch, 26 gauge needle. The opposite thigh was injected in thesame manner using a saline placebo of identical appearance in a blindedfashion. The injections were repeated three times a week for four weeks,and the thigh circumference was measured at the level of the injectionsat the beginning and at the end of the four-week treatment period. Thewomen were encouraged to exercise by walking and to adhere to a balanceddiet restricted to 20 kcal/kg of desirable body weight, or about 1200calories per day. Four of the five women outpatients lost body weightduring the four week treatment period, and all four of these women lostmore girth from the thigh treated with isoproterenol injections. Thegirth changes in the four women who lost weight were 5cm, 2.5cm, 1cm and1cm, respectively, where girth change is defined as the decreased girthon the treated thigh minus the decreased girth on the untreated thigh.The fifth woman gained 1/2 pound during the four week treatment period,and had equal amounts of girth change on her thighs bilaterally.

It will now be appreciated that, through the use of this invention,accelerated weight reduction from regional fat deposits may beaccomplished during a general weight control program. The selectiveweight loss from regional fat deposits allows the accelerated reductionof weight and size from those regional fat deposits which ordinarily arereduced more slowly in a weight control program. Consequently, abalanced weight reduction may be achieved, so that normally slowlyreducing portions of the body, such as the thighs, may be reduced at arate comparable with that of the naturally more rapidly reducingportions, such as the abdomen.

Although a particular embodiment of the invention is described in detailfor purposes of illustration, various embodiments may be made withoutdeparting from the spirit and the scope of the invention. Accordingly,the invention is not to be limited, except as by the appended claims.

I claim:
 1. A process for achieving a selective reduction in bodyweight, comprising the steps of:delivering specifically to the portionof the body where weight reduction is sought a therapeutically effectiveamount of a beta adrenergic stimulator and accomplishing a generalweight loss program whereby an acceleration of weight loss is achievedfrom the portion of the body to which the beta adrenergic stimulator wasselectively delivered.
 2. The process of claim 1, wherein said deliverystep is achieved by injection.
 3. The process of claim 1, wherein thebeta adrenergic stimulator is specifically delivered to the thighs. 4.The process of claim 1, wherein said delivery step is achieved bytopical application to the surface of the skin.
 5. The process of claim1, wherein the beta adrenergic stimulator is isoproterenol.
 6. Theprocess of claim 1, wherein the beta adrenergic stimulator introducedspecifically into the portion of the body where weight reduction issought is selected from the group consisting of theophylline,isoproterenol, forskolin and epinephrine.
 7. A process for acceleratedreduction of a regional fat deposit present in a selected portion of thebody, comprising the steps of:introducing specifically into the regionalfat deposit a therapeutically effective amount of a beta adrenergicstimulator and undergoing a program of general weight reduction.
 8. Theprocess of claim 6, wherein the beta adrenergic stimulator is selectedfrom the group consisting of theophylline, isoproternol, forskolin andepinephrine.
 9. The process of claim 6, wherein said introducing step isaccomplished by injection.
 10. The process of claim 6, wherein saidintroducing step is accomplished by topical application to the surfaceof the skin.
 11. A process for accelerating the reduction of regionalfat deposits in a person undergoing a program of treatment for anoverweight condition, comprising the step of:delivering specifically tothe portion of the person's body where weight reduction is sought atherapeutically effective amount of a beta adrenergic stimulator. 12.The process of claim 11, wherein said step of delivering is accomplishedby injection.
 13. The process of claim 11, wherein said step deliveringis accomplished by topical application to the surface of the skin. 14.The process of claim 11, wherein the portion of the body where weightreduction is sought is the thighs, and the beta adrenergic stimulator isdelivered to the thighs.
 15. The process of claim 11, wherein theportion of the body where weight reduction is sought is the legs, andthe beta adrenergic stimulator is delivered to the legs.
 16. The processof claim 11, wherein the beta adrenergic stimulator is selected from thegroup consisting of theophylline, isoproterenol, forskolin, andepinephrine.